Class III antiarrhythmic agents may be categorized as having the ability to markedly prolong Purkinje fiber action potential duration without producing significant changes in maximal upstroke velocity. Unlike Class I antiarrhythmic agents, a pure Class III agent displays no effect on cardiac sodium channels. The electrophysiologic properties of a compound possessing a Class III activity profile are observed in vivo as negligible effects on atrial, ventricular and H-V conduction times while producing a marked increase (greater than 20 percent) in both the atrial and ventricular refractory period. In contrast, Class I agents will demonstrate a marked slowing of ventricular conduction velocity, with variable effects on the refractory period. Recent reviews of these agents are by: Brexton et al., Pharmac. Ther. 17, 315-55 (1982); Vaughan-Williams, J. Clin. Pharmacol. 24, 129-47 (1984); Steinberg et al., Ann. Rep. Med. Chem. 21, 95-108 (1986).
The following workers have reported the selective Class III antiarrhythmic activity of the dextro enantiomer of 4-(2-isopropylamino-1-hydroxyethyl)-methane-sulfonamide (MJ-1999, Sotalol): Taggart, et al., Clin. Sci. 69, 631-636 (1985) and McComb, et al., J. Am. Coll. Cardiol. 5, 438 (1985).
Silberg et al., ACAD Rep. Populace Romire, Fillala Clug, Studee Cercetari Med., 10244-52 (1959) disclose p-acetylamino-N-(2-diethylaminoethyl)benzenesulfonamide and compare its antiarrhythmic properties with procainamide.
Wohl et al. disclose N-[2-(diethylamino)ethyl]-4-[(methylsulfonyl)amino]-benzamide hydrochloride as a potential class III antiarrhythmic agent in U.S. Pat. No. 4,544,654, Oct. 1, 1985.
Cross et al. have reported various (phenyl(carbonyl)alkyl)-4-(pyridinyl or imidazolyl)piperazines as useful antiarrhythmic agents in European Patent 0233051, June 19, 1987. A series of phenylpiperazinyl-propranol derivatives are disclosed in U.S. Pat. 4,428,950 by Franke et al., however, the antiarrhythmic activity (if any) is not discussed.